Avian species have a unique organ development pattern compared to mammals. Birds expend a very high percentage of their initial energy supply on early development of the supply organs (those organs that supply nutrients and oxygen for survival), especially the digestive tract. Indeed on a per unit of body weight basis, neonatal domestic poultry have a larger gastrointestinal tract than most species. Lilja and Marks, Growth, Development and Aging 55, 219 (1991). Paradoxically, the functional development of the gastrointestinal tract (i.e. the ability to digest and absorb nutrients) occurs at a slower rate than gut growth in turkeys. Liu, Comparison of sucrase, maltase and alkaline phosphatase activities in embryonic duodena between domestic and wild turkeys, M. S. Thesis, North Carolina State University (1991). This is of great concern since in the modern broiler chick it has been shown that the ability to absorb glucose from the intestinal tract is barely able to meet demands necessary for growth. Obst and Diamond, Auk. 109, 451 (1992). This has been interpreted by Croom et al., J. Dairy Sci., 71, 2112 (1993), to suggest that intestinal absorption may be limiting the phenotypic expression of the genetic potential of modern livestock and poultry. Fan found that selection for rapid growth in turkeys did not result in concomitant improvements in the rate or efficiency of glucose absorption from the jejunum, suggesting that the nutrient absorption by the gut is rate-limiting for growth. Fan, Ph.D. Dissertation, Effect of Genetic Selection on Energetic Efficiency of Small Intestinal Glucose Absorption, Department of Animal Science, North Carolina State University (1994). Similar findings have been reported for high egg production chickens by Majumdar and Panda, Indian J. Anim. Sci. 64, 1165 (1994).
Recent studies at North Carolina State University have demonstrated that the development of intestinal function in the hatchling of the modern domestic turkey is delayed relative to their wild ancestors. Coles et al., FASEB J. 7, A588 (1993). Other findings suggest that genetic selection for growth, feed efficiency and muscling may have resulted in unforseen decreases in the ability of the young poult to digest and absorb feedstuffs. Failure to assimilate and absorb vital nutrients at a young age, when systems important to survival (immune and digestive) are at a critical stage of development, may place a weakened hatchling at a higher risk for early death from disease.
In particular, mortality of neonate turkeys is greater than in most other poultry species. Mortality of unknown etiology accounts for nearly 50% of all management-related deaths in the U.S. turkey industry (Minnesota Statistical Reporting Service). On the average, 2 to 5% of all poults placed in brooder houses in the United States die of unknown causes before they begin to grow. The etiology of this occurrence is unknown. Poults dying without a known cause have been given the name of "starveouts" by some industry personnel because they appear weak and emaciated. In 1995, approximately 360 million turkeys were produced in the United States. If there is a 2% loss to unknown causes with an average market weight of 25 lbs with a value of $0.40 per pound, this loss costs turkey producers $72 million dollars a year.
An additional cause of hatchling mortality in the turkey industry has been the sudden and devastating appearance of the disease Poult Enteritis Mortality Syndrome (PEMS). The onset of this disease in young turkeys is characterized by severe flushing followed by very high death rates which peak at about two weeks of age. Barnes et al., Poult Enteritis Mortality Syndrome (Spiking Mortality of Turkeys) and Related Disorders--Update, Technical White Paper, Department of Poultry Science, North Carolina State University (1995). Those birds that do survive have severely depressed growth and are sometimes unsalvageable. The cause of this phenomenon is unknown. The increasing frequency of its occurrence is rapidly adding to the amount of monies loss by the industry to events associated with neonatal death.
Recently, Croom and colleagues have demonstrated that the exogenous administration of epidermal growth factor (EGF) and Peptide YY (PYY) increases glucose absorption in young growing mice. Bird et al., J. Anim. Sci., 2523 (1996); Bird et al., J. Nutr. 124, 231 (1994). Both of these peptides are active orally. PYY has previously been shown to delay gastric emptying and intestinal transit time and to decrease pancreatic enzyme secretion. Savage et al., Gut, 28, 166 (1987); Pironi et al., Gastroenterology 105, 733 (1993); Adrian et al. Gastroenterology 89, 494 (1985). Of particular interest is the ability of PYY to increase glucose absorption without corresponding increases in the energetic cost of digestion. Bird et al., J. Anim. Sci., 2523 (1996). This should result in an increase in net energy absorbed. This technology is currently the subject of co-pending U.S. patent application No. 08/379,354 to Croom et al. Other scientists have shown that both EGF and PYY increase intestinal absorption of amino acids (Schwartz and Storozuk, Amer. J. Surg. 155, 18 (1988)) and fat (Kalogeris et al., Gastro. 110, A809 (1996)).
Accordingly, the present invention addresses an unmet need for new technologies for preventing and/or attenuating the effects of various causes of neonatal mortality in birds. In particular, disclosed herein are methods of enhancing precocial development of the digestive tract of hatchlings prior to hatching so that the young bird is better able to benefit from high quality nutrition and management strategies resulting in healthier and thriftier birds.